In 2003, WHO reported that approximately 22 millions of world population carry cancers. Cancers takes the second ranking (12%) next to cardiovascular diseases among all diseases in terms of the death rate with respect to the incidence rate. Especially, in advanced countries, the number of deaths due to cancers reaches about 2.5 million, accounting for about 21% of total deaths. In the future, it is expected that the incidence rate of cancers will rapidly increase by nearly 50% every year. In the Republic of Korea, the increase rate is about 10% a year, as of 2001. Before 1970s, most diseases in the Republic of Korea were caused by bacterial infections, insufficient nutrition, etc, however, incidence of cancers shows a tendency to increase continuously due to the economic growth and Westernized dietary life. Especially, it is known that colon cancer is more closely connected with the change of the dietary life than other cancers. At present, colon cancer increases at high speed and is a representative cancer, accounting for 11.2% of total cancers in the Republic of Korea.
GA733-2 (TACSTD1: tumor-associated calcium signal transducer 1, GenBank GeneID 4072) is a 40 kDa surface glycoprotein expressed in all epithelial cells. It is known to act as a homotypic calcium-independent cell adhesion molecule, and especially to be overexpressed in cancer cells. Especially, the amount of GA733-2 expressed in colon cancer cells remarkably differs from that in normal colon cells, as compared to other internal organ cells. A monoclonal antibody for GA733-2 is used for treating colon cancer.
In order to identify the cause of cancers, especially colon cancer, and to develop therapeutic agents therefor, the development of an animal model for controlling the expression of GA733-2 is necessary to perform experiments prior to clinical trials. In this regard, an animal model for inflammatory bowel disease (IBD) has been used as the model for colon cancer. However, an experimental mouse model for colon cancer to control the expression of GA733-2 has not yet been developed.
Meanwhile, it has been known in the art that TREM-2 (Triggering Receptor Expressed on Myeloid cells-2; Genbank Accession No. AK039477) plays a role of controlling the function of myeloid cells as a receptor transferring a signal via an adaptor protein DAP12. Moreover, in vitro experiments showed that TREM-2 derived from a microorganism suppresses an inflammatory reaction by inhibiting the expression of cytokines, suggesting that it involves in the immune regulation. However, it has not been clearly identified a role of TREM-2 in an immune system through in vivo experiments, since a probe for TREM-2 has not been developed.
The present inventors have found out that TREM-2 gene is specifically expressed with a high copy number only in progenitor cells of natural killer cells through serial analysis of gene expression (SAGE), and suggested that TREM-2 would have influence on differentiation into natural killer cells and activities thereof. Therefore, the inventors have cloned TREM-2 gene and manufactured a TREM-2-IgG fusion protein and filed a patent application therefor (Korean Patent Publication No. 2006-135280). However, it has never been known that TREM-2 involves in controlling the expression of GA733-2 associated with cancers, especially colon cancer. Further, a transgenic animal transformed with TREM-2, and capable of controlling the expression of GA733-2 has never been produced.